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The LncRNA signature associated with cuproptosis as a novel biomarker of prognosis in immunotherapy and drug screening for clear cell renal cell carcinoma

Cuproptosis is a new form of cell death, the second form of metal ion-induced cell death defined after ferroptosis. Recently, cuproptosis has been suggested to be associated with tumorigenesis. However, the relationship between cuproptosis and patient prognosis in clear cell renal cell carcinoma (cc...

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Autores principales: Zhang, Lishuo, Di, Longjiang, Liu, Jinhui, Lei, Xianli, Gu, Maoli, Zhang, Wenjing, Wang, Yufu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9899836/
https://www.ncbi.nlm.nih.gov/pubmed/36755568
http://dx.doi.org/10.3389/fgene.2023.1039813
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author Zhang, Lishuo
Di, Longjiang
Liu, Jinhui
Lei, Xianli
Gu, Maoli
Zhang, Wenjing
Wang, Yufu
author_facet Zhang, Lishuo
Di, Longjiang
Liu, Jinhui
Lei, Xianli
Gu, Maoli
Zhang, Wenjing
Wang, Yufu
author_sort Zhang, Lishuo
collection PubMed
description Cuproptosis is a new form of cell death, the second form of metal ion-induced cell death defined after ferroptosis. Recently, cuproptosis has been suggested to be associated with tumorigenesis. However, the relationship between cuproptosis and patient prognosis in clear cell renal cell carcinoma (ccRCC) in the context of immunotherapy remains unknown. The aim of this study was to investigate the correlation between cuproptosis-related long non-coding RNA (lncRNA) and ccRCC in terms of immunity as well as prognosis. Clinical information on lncRNAs associated with differences in cuproptosis genes in ccRCC and normal tissues was collected from The Cancer Genome Atlas (TCGA) dataset. Univariate Cox regression was used to screen lncRNAs. A total of 11 lncRNAs closely associated with cuproptosis were further screened and established using the least absolute shrinkage and selection operator (LASSO) algorithm and multivariate Cox regression, and the samples were randomly divided into training and test groups. A risk prognostic model was constructed using the training group, and the model was validated using the test group. We investigated the predictive ability of the prognostic risk model in terms of clinical prognosis, tumor mutation, immune escape, immunotherapy, tumor microenvironment, immune infiltration levels, and tumor drug treatment of ccRCC. Using the median risk score, patients were divided into low and high-risk groups. Kaplan-Meier curves showed that the overall survival (OS) of patients in the high-risk group was significantly worse than low-risk group (p < 0.001). Receiver operating characteristic (ROC) curves further validated the reliability of our model. The model consistently and accurately predicted prognosis at 1, 3, and 5 years, with an AUC above 0.7. Tumor cell genes generally precede morphological abnormalities; therefore, the model we constructed can effectively compensate for the traditional method of evaluating the prognosis of patients with renal cancer, and our model was also clinically meaningful in predicting ccRCC staging. In addition, lower model risk scores determined by mutational load indicated a good chance of survival. The high-risk group had greater recruitment of immune cells, while the anti-immune checkpoint immunotherapy was less efficacious overall than that of the low-risk group. Tumor and immune-related pathways were enriched, and anti-tumor agents were selected to improve the survival of ccRCC. This prognostic risk model is based on the levels of cuproptosis-associated lncRNAs and provides a new perspective in the clinical assessment and precise treatment of ccRCC.
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spelling pubmed-98998362023-02-07 The LncRNA signature associated with cuproptosis as a novel biomarker of prognosis in immunotherapy and drug screening for clear cell renal cell carcinoma Zhang, Lishuo Di, Longjiang Liu, Jinhui Lei, Xianli Gu, Maoli Zhang, Wenjing Wang, Yufu Front Genet Genetics Cuproptosis is a new form of cell death, the second form of metal ion-induced cell death defined after ferroptosis. Recently, cuproptosis has been suggested to be associated with tumorigenesis. However, the relationship between cuproptosis and patient prognosis in clear cell renal cell carcinoma (ccRCC) in the context of immunotherapy remains unknown. The aim of this study was to investigate the correlation between cuproptosis-related long non-coding RNA (lncRNA) and ccRCC in terms of immunity as well as prognosis. Clinical information on lncRNAs associated with differences in cuproptosis genes in ccRCC and normal tissues was collected from The Cancer Genome Atlas (TCGA) dataset. Univariate Cox regression was used to screen lncRNAs. A total of 11 lncRNAs closely associated with cuproptosis were further screened and established using the least absolute shrinkage and selection operator (LASSO) algorithm and multivariate Cox regression, and the samples were randomly divided into training and test groups. A risk prognostic model was constructed using the training group, and the model was validated using the test group. We investigated the predictive ability of the prognostic risk model in terms of clinical prognosis, tumor mutation, immune escape, immunotherapy, tumor microenvironment, immune infiltration levels, and tumor drug treatment of ccRCC. Using the median risk score, patients were divided into low and high-risk groups. Kaplan-Meier curves showed that the overall survival (OS) of patients in the high-risk group was significantly worse than low-risk group (p < 0.001). Receiver operating characteristic (ROC) curves further validated the reliability of our model. The model consistently and accurately predicted prognosis at 1, 3, and 5 years, with an AUC above 0.7. Tumor cell genes generally precede morphological abnormalities; therefore, the model we constructed can effectively compensate for the traditional method of evaluating the prognosis of patients with renal cancer, and our model was also clinically meaningful in predicting ccRCC staging. In addition, lower model risk scores determined by mutational load indicated a good chance of survival. The high-risk group had greater recruitment of immune cells, while the anti-immune checkpoint immunotherapy was less efficacious overall than that of the low-risk group. Tumor and immune-related pathways were enriched, and anti-tumor agents were selected to improve the survival of ccRCC. This prognostic risk model is based on the levels of cuproptosis-associated lncRNAs and provides a new perspective in the clinical assessment and precise treatment of ccRCC. Frontiers Media S.A. 2023-01-23 /pmc/articles/PMC9899836/ /pubmed/36755568 http://dx.doi.org/10.3389/fgene.2023.1039813 Text en Copyright © 2023 Zhang, Di, Liu, Lei, Gu, Zhang and Wang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Zhang, Lishuo
Di, Longjiang
Liu, Jinhui
Lei, Xianli
Gu, Maoli
Zhang, Wenjing
Wang, Yufu
The LncRNA signature associated with cuproptosis as a novel biomarker of prognosis in immunotherapy and drug screening for clear cell renal cell carcinoma
title The LncRNA signature associated with cuproptosis as a novel biomarker of prognosis in immunotherapy and drug screening for clear cell renal cell carcinoma
title_full The LncRNA signature associated with cuproptosis as a novel biomarker of prognosis in immunotherapy and drug screening for clear cell renal cell carcinoma
title_fullStr The LncRNA signature associated with cuproptosis as a novel biomarker of prognosis in immunotherapy and drug screening for clear cell renal cell carcinoma
title_full_unstemmed The LncRNA signature associated with cuproptosis as a novel biomarker of prognosis in immunotherapy and drug screening for clear cell renal cell carcinoma
title_short The LncRNA signature associated with cuproptosis as a novel biomarker of prognosis in immunotherapy and drug screening for clear cell renal cell carcinoma
title_sort lncrna signature associated with cuproptosis as a novel biomarker of prognosis in immunotherapy and drug screening for clear cell renal cell carcinoma
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9899836/
https://www.ncbi.nlm.nih.gov/pubmed/36755568
http://dx.doi.org/10.3389/fgene.2023.1039813
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